Aengus Officer

• Lindeman, Ida; Officer, Aengus; Dahal-Koirala, Shiva; Risnes, Louise Fremgaard; Hjort, Rebecka & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2026). A predisposing effect of HLA class II genes in celiac disease by skewing the naive CD4⁺T cell receptor repertoire. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 123(26). doi: 10.1073/pnas.2520636123. Fulltekst i vitenarkiv
• Officer, Aengus; Watson, Corey T.; Engelbrecht, Eric; Dahal-Koirala, Shiva; Risnes, Louise Fremgaard & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2026). Immunoglobulin gene polymorphisms shape the naïve B-cell receptor repertoire; relevance to celiac disease. Genes and Immunity. ISSN 1466-4879. 27, s. 210–222. doi: 10.1038/s41435-026-00384-4. Fulltekst i vitenarkiv

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• Officer, Aengus (2026). Genetic effects on the naive adaptive immune receptor repertoire in coeliac disease. Universitetet i Oslo. ISSN 9788234808593. Fulltekst i vitenarkiv Vis sammendrag

  Adaptive immunity relies on the diverse repertoires of B cell and T cell receptors (BCRs and TCRs) which are generated through V(D)J recombination and also shaped by germline genetic variation. Inherited polymorphisms and structural variants within immunoglobulin (IG) and TCR loci influence receptor gene usage and contribute substantially to inter-individual repertoire variation. Coeliac disease (CeD), a genetically well-characterised immune-mediated disorder strongly associated with HLA class II allotypes (particularly HLA-DQ2.5), provides a model to investigate how these inherited effects shape disease-relevant immune repertoires. In this thesis work, sequencing of naïve BCR and TCR repertoires from approximately 100 individuals with CeD and 100 controls was integrated with dense genotyping to characterise genetic influences on the naïve repertoire. Widespread cis-acting associations between germline variants and IG gene usage were identified across heavy and light chain loci. However, no CeD-specific differences in naïve BCR gene usage were observed. By contrast, naïve CD4+ TCR gene usage showed a more complex architecture, shaped by both cis-acting variants and strong trans-acting effects from the HLA region. HLA-DQ2.5 was associated with increased usage of TCR V genes linked to gluten reactivity, explaining the higher usage observed in CeD. Machine learning analyses confirmed that TCR repertoire-based classification was driven primarily by HLA rather than disease status. Overall, this work demonstrates that germline genetic variation – particularly HLA – influences the composition of naïve adaptive immune receptor repertoires.

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